E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatic cyst, solitary or dominant |
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E.1.1.1 | Medical condition in easily understood language |
Patients with a large hepatic cyst |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to minimize fluid reaccumulation in the hepatic cyst after aspiration sclerotherapy in order to reduce cyst size. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to reduce symptoms, improve health-related quality of life, and recude liver cyst recurrence to prevent re-interventions. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Population:
All patients who are diagnosed with a dominant liver cyst with an indication for aspiration and sclerotherapy are suitable for inclusion in this study.
Inclusion criteria:
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age 18 - 70 years
- Indication for aspiration and sclerotherapy
- Providing informed consent
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study:
ASPIRATION SCLEROTHERAPY RELATED EXCLUSION CRITERIA
1. Signs of cyst bleeding on ultrasound
2. Signs of cyst infection (elevated CRP and/or leukocytes or temperature exceeding 38 degrees with the exclusion of a different focus)
3. Cyst < 5 cm
4. Coagulopathy (INR > 2 or platelets < 80 x 10^9 )
5. Severe co-morbidity contraindicating anesthesia (i.e. ASA 4 classification)
SOMATOSTATIN TREATMENT RELATED EXCLUSION CRITERIA
6. Patients with a known hypersensitivity to SST analogues or any component of the pasireotide LAR or SQ formulations
7. Pregnant or nursing women
8. Symptomatic cholecystolithiasis
9. QT interval related exclusion criteria:
9.1 Known (congenital) long QT syndrome or QTcF at screeningg > 470 msec
9.2 Family history of long QT syndrome or idiopathic sudden death
9.3 Uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina or sustained and/or clinically significant cardiac arrhythmias (e.g. bradycardia)
9.4 Risk factors for torsades de pointes: hypokalemia, hypomagnesemia, hypocalcaemia, cardiac failure, clinically significant/symptomatic bradycardia, or high grade AV block
9.5 Patients with concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
9.6 Taking anti-arrhythmic medicinal products or other substances that are known to lead to QT prolongation
10. Uncontrolled diabetes as defined by HbA1C >8% despite adequate therapy
12. History of pancreatitis
13. Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment
FURTHERMORE:
14. Use of oral contraception or estrogen supplementation
15. Intervention (i.e. aspiration with or without sclerotherapy or surgical intervention) within six months before baseline
16. Treatment with somatostatin analogues within six months before baseline
17. Treatment with other experimental (i.e. non marketed) therapies, within 1 month prior to dosing
18. Any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the proportional change (%) in cyst diameter as measured by ultrasound at the baseline visit versus the diameter obtained at 4 weeks after aspiration sclerotherapy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks after aspiration sclerotherapy |
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E.5.2 | Secondary end point(s) |
Liver end points:
1. The absolute cyst reduction in centimeters as measured by ultrasound at the baseline visit versus 4 weeks after aspiration sclerotherapy.
2. The proportional change and absolute cyst reduction as measured by ultrasound at the baseline visit versus 12 weeks after aspiration sclerotherapy.
3. The proportion (%) of patients having cyst recurrence (> 80% of its original diameter) as measured by ultrasound 12 weeks after aspiration sclerotherapy.
Patient reported outcome measures:
4. Change of symptoms using a PLD-related symptoms questionnaire, assessed at the baseline visit versus the value obtained at 4 and 12 weeks after aspiration sclerotherapy.
5. Change of health-related quality of live using the MOS SF-36 questionnaire, assessed at the baseline visit versus the value obtained at 4 and 12 weeks after aspiration sclerotherapy.
Complications or adverse events
6. Any complications or adverse events during procedure or follow-up.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See secondary end points for timepoints |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |